The JHHCC, established in 1989, has been a premier source of HIV longitudinal research with over 250 manuscripts published on the risk factors and outcomes of HIV infection. Almost half of the JHHCC are patients with a history of injecting drug use (IDU), enabling us to conduct studies that directly compare receipt, adherence and clinical outcomes of HIV care between IDU and non-IDU patients from the same geographic and socioeconomic catchment areas of an Eastern city that has a high prevalence and incidence of HIV infection. HIV infection remains at epidemic levels in Baltimore, and substance use is a co-epidemic that is a barrier to receipt and continuity of effective HIV medical care. During the over two-decade existence of the JHHCC, the HIV epidemic in the U.S. has undergone a remarkable evolution. Current antiretroviral therapy (ART) is highly effective in suppressing virus and there has been a dramatic decline in AIDS-related disease and improvement in life-expectancy. However, there is growing evidence of an increased risk for the development of a number of HIV-associated non-AIDS (HANA) comorbidities such as cardiovascular, renal, liver, metabolic and malignant disease. Although controversial, the concept of premature aging from HIV infection is a concern. Our first Aim will build upon our strengths in longitudinal research focusing on HIV progression, HANA and aging with HIV infection. Another focus of the JHHCC has been viral hepatitis co-infection, particularly hepatitis C, a comorbidity that is prevalent in 45% of our patients, principally because of IDU. There have been substantial barriers to effective hepatitis C treatment in our population, but again, an evolution in therapy is occurring. Novel direct-acting antiviral drugs are rapidly becoming available that appear to be simpler to use and more effective in achieving a sustained virologic response. Our second Aim will focus on utilization, adherence, barriers and outcomes of these promising new therapies. Finally, the JHHCC has a proven history of collaboration with over 150 epidemiological, clinical, translational and health services investigators by providing existing data, adding new data collection methods and instruments, identifying patient phenotypes for pathogenesis studies, clinical trials and observational studies, supplying repository specimens and serving as a research platform for a variety of investigational interests. Our third Aim is to expand our collaborations with investigators who would benefit from the resources of the JHHCC.